title: Human endometrial mesenchymal stem cells modulate the tissue response and mechanical behavior of polyamide mesh implants for pelvic organ prolapse repair.
abstract: BACKGROUND
  Pelvic organ prolapse (POP) is defined as the descent of one or more of the pelvic structures into the vagina and includes uterine, vaginal vault, and anterior or posterior vaginal wall prolapse. The treatment of POP may include implantation of a synthetic mesh. However, the long-term benefit of mesh surgery is controversial due to complications such as mesh exposure or pain. The aim of this study was to use a tissue engineering (TE) approach to assess the in vivo biological and biomechanical behavior of a new gelatin/polyamide mesh, seeded with a novel source of mesenchymal stem cells in a subcutaneous rat model of wound repair.
  
  
  METHODS
  W5C5-enriched human endometrial mesenchymal stem cells (eMSC) were seeded onto meshes (gelatin-coated polyamide knit) at 100,000 cells/cm². Meshes, with or without cells were subcutaneously implanted dorsally in immunocompromised rats for 7, 30, 60, and 90 days. Flow cytometry was used to detect DiO labeled cells after explantation. Immunohistochemical assessment of foreign body reaction and tissue integration were conducted. Total collagen and the levels of collagens type III and type I were determined. Uniaxial tensiometry was performed on explanted meshes, originally seeded with and without cells, at days 7 and 90.
  
  
  RESULTS
  Implanted meshes were well tolerated, with labeled cells detected on the mesh up to 14 days postimplantation. Meshes with cells promoted significantly more neovascularization at 7 days (p<0.05) and attracted fewer macrophages at 90 days (p<0.05). Similarly, leukocyte infiltration was significantly lower in the cell-seeded meshes at 90 days (p<0.05). Meshes with cells were generally less stiff than those without cells, after 7 and 90 days implantation.
  
  
  CONCLUSIONS
  The TE approach used in this study significantly reduced the number of inflammatory cells around the implanted mesh and promoted neovascularization. Seeding with eMSC exerts an anti-inflammatory effect and promotes wound repair with new tissue growth and minimal fibrosis, and produces mesh with greater extensibility. Cell seeding onto polyamide/gelatin mesh improves mesh biocompatibility and may be an alternative option for future treatment of POP.
authors.affiliation: 1 The Ritchie Centre, Monash Institute of Medical Research , Clayton, Victoria, Australia .
authors.forename: Daniela
authors.initials: D
authors.lastname: Ulrich
authors.forename: Sharon Lee
authors.initials: SL
authors.lastname: Edwards
authors.forename: Kai
authors.initials: K
authors.lastname: Su
authors.forename: Ker Sin
authors.initials: KS
authors.lastname: Tan
authors.forename: Jacinta F
authors.initials: JF
authors.lastname: White
authors.forename: John A M
authors.initials: JA
authors.lastname: Ramshaw
authors.forename: Camden
authors.initials: C
authors.lastname: Lo
authors.forename: Anna
authors.initials: A
authors.lastname: Rosamilia
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Werkmeister
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Gargett
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004717:Endometrium / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005549:Foreign-Body Reaction / Q000473:pathology; D005780:Gelatin / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009757:Nylons / Q000494:pharmacology*; D056887:Pelvic Organ Prolapse / Q000473:pathology / Q000628:therapy*; D019736:Prostheses and Implants; D019919:Prosthesis Implantation; D051381:Rats; D034421:Sus scrofa; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D009757:Nylons; C009930:polyamide mesh; D005780:Gelatin; D003094:Collagen; D017493:Leukocyte Common Antigens